Evidence map›Paper›PMID 39755643›Full record

ReviewJournal of translational medicine2025

From ex vivo to in vivo chimeric antigen T cells manufacturing: new horizons for CAR T-cell based therapy.

E Pinto, L Lione, M Compagnone, M Paccagnella, E Salvatori, M Greco, V Frezza, E Marra, L Aurisicchio, G Roscilli and 1 more

Abstract readReview
In one paragraph

Review in Journal of translational medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 63 papers.

0numbers the graph read from it
0cells of the map it votes in
63citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

63 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. Article
  6. Article
  7. Review
  8. Nanomaterials Drive In Vivo CAR Immune Cells Engineering.Advanced materials (Deerfield Beach, Fla.) · 2026
    Review
  9. The evolution of cellular-based immunotherapy in the treatment of gastric cancer: an overview of clinical trials.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  10. Review
  11. Review
  12. Review
  13. Emerging strategies to reduce the side effects of CAR-T cell therapy: focusing on gene editing and nanotechnology.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026
    Review
  14. Review
  15. Review
  16. Review
  17. Review
  18. Review
  19. Adoptive T-cell therapies in the clinic.Bioengineering & translational medicine · 2026
    Review
  20. In Vivo T-Cell Engineering: Revolution in Delivery Strategies and Clinical Translation.BioDrugs : clinical immunotherapeutics, biopharmaceuticals and gene therapy · 2026
    Review

3 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

11 authors.

E PintoEvvivax Biotech, Via Castel Romano 100, 00128, Rome, Italy.
L LioneTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
M CompagnoneEvvivax Biotech, Via Castel Romano 100, 00128, Rome, Italy.
M PaccagnellaTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
E SalvatoriTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
M GrecoTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
V FrezzaTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
E MarraTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
L AurisicchioEvvivax Biotech, Via Castel Romano 100, 00128, Rome, Italy.
G RoscilliTakis Biotech, Via Castel Romano 100, 00128, Rome, Italy.
A ConfortiEvvivax Biotech, Via Castel Romano 100, 00128, Rome, Italy. conforti@takisbiotech.it.ORCID 0000-0001-8524-5936

Funding

Ministero dell'Istruzione, dell'Università e della Ricerca CN3-National center for gene therapyMinistero dell'Istruzione, dell'Università e della Ricerca drugs based on RNA technology
6 · The paper itself

Abstract

In the past decades, Chimeric Antigen Receptor (CAR)-T cell therapy has achieved remarkable success, leading to the approval of six therapeutic products for haematological malignancies. Recently, the therapeutic potential of this therapy has also been demonstrated in non-tumoral diseases. Currently, the manufacturing process to produce clinical-grade CAR-T cells is complex, time-consuming, and highly expensive. It involves multiple steps, including the collection of T cells from patients or healthy donors, in vitro engineering and expansion, and finally reinfusion into patients. Therefore, despite the impressive clinical outcomes, ex vivo manufacturing process makes CAR-T cells out of reach for many cancer patients. Direct in vivo engineering of T cells could be a more rapid solution able to circumvent both the complexity and the costs associated with ex vivo manufactured CAR-T cells. This novel approach allows to completely eliminate ex vivo cell manipulation and expansion while producing therapeutic cell populations directly in vivo. To date, several studies have demonstrated the feasibility of in vivo T cell reprogramming, by employing injectable viral- or nanocarrier-based delivery platforms in tumour animal models. Additionally, in vivo production of CAR-T cells might reduce the incidence, or at least the severity, of systemic toxicities frequently occurring with ex vivo produced CAR-T cells, such as cytokine release syndrome and immune effector cell-associated neurotoxicity syndrome. In this review, we highlight the challenges associated with the current ex vivo manufacturing protocols and review the latest progresses in the emerging field of in vivo CAR-T therapy, by comparing the various platforms so far investigated. Moreover, we offer an overview of the advantages deriving from in vivo reprogramming of other immune cell types, such as Natural Killer and macrophages, with CAR constructs.

Indexed as

Receptors, Chimeric AntigenT-LymphocytesAnimalsCell- and Tissue-Based TherapyHumansImmunotherapy, AdoptiveReceptors, Chimeric AntigenCAR T cellManufacturingT cell engineering

Identifiers

PMID39755643
PMCPMC11700462

What OpenQuestion holds

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LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.